Project Summary The goal of this work is to develop a fundamental understanding of the translational regulation of T regulatory cell (Treg) development, of which very little is known, which can inform the development of more effective therapeutic approaches to the regulation of Tregs in human cancer and autoimmune disease. Our research has provided important insights into the molecular regulation of selective mRNA translation in Treg development which we ultimately seek to capitalize on in generation of more effective immune-based therapies. This work is directed to understanding and then targeting the privileged translation of Treg fate determining mRNAs. The objective of our research is to determine the mechanism at the level of translational control which key Treg mRNAs promote Treg development and immune suppression functions.

Project Narrative This grant application seeks to develop an understanding the translational regulation of immune suppressive and tumor promoting T regulatory cell development. Based on our ongoing research, we propose to understand the mechanism by which preferential translation of fate determining T regulatory cell mRNAs orchestrate development and activation of immune suppressing Tregs.